COPD (Chronic Obstructive Pulmonary Disease)

November 7, 2016

Theravance Biopharma and Mylan released results of two replicate phase III efficacy studies of revefenacin (TD-4208) for chronic obstructive pulmonary disease (COPD). The randomized, double-blind, placebo-controlled, parallel-group studies enrolled over 1,250 patients. Study investigators tested two doses (88mcg and 175mcg) of revefenacin inhalation solution. The trials demonstrated statistically and clinically relevant increases in trough forced expiratory volume in one second (FEV1) after 12 weeks of once-daily dosing. The improvements in trough FEV1 compared to placebo for the intent-to-treat population across both studies were 118mL and 145mL for 88mcg and 175mcg, respectively. In pre-specified pooled analyses, revefenacin produced increases in trough FEV1 in the subgroup (38%) of patients using background long-acting beta agonist (LABA) containing therapies and in the subgroup of patients who were not using concomitant LABA therapy. The improvements in FEV1 for the LABA subgroup were 92mL and 135mL for 88mcg and 175mcg, respectively, and for the non-LABA subgroup were 131mL and 150mL for 88mcg and 175mcg, respectively. The revefenacin program includes an ongoing twelve-month, open-label, active comparator safety study in more than 1,050 patients, which is expected to be completed in 2017. Should outcomes from the safety study be supportive, Theravance Biopharma expects to file an NDA for revefenacin with the FDA by the end of 2017.

July 11, 2016

GlaxoSmithKline and Innoviva released results of a phase III study of Closed Triple (the combination of fluticasone furoate (FF), umeclidinium (UMEC) and vilanterol (VI)) in patients with chronic obstructive pulmonary disease (COPD). The FULFIL study compared FF/UMEC/VI with budesonide and formoterol, an ICS/LABA combination delivered twice-daily in the Turbohaler dry powder inhaler. The FULFIL study met its two co-primary endpoints, demonstrating statistically significant improvements compared with twice-daily Symbicort Turbohaler (budesonide/formoterol 400/12mcg) in both lung function as measured by trough FEV1 (171mL, 95% confidence interval [148, 194] p<0.001), and health-related quality of life as measured by the St. George’s Respiratory Questionnaire (SGRQ) (-2.2 units, 95% confidence interval [-3.5, -1.0] p<0.001), at the end of the 24-week study period. The proportion of patients who responded with the minimum clinically important difference in SGRQ (-4 units) was 50% on FF/UMEC/VI and 41% on budesonide/formoterol. Findings support plans to submit regulatory filings for the approval of the Closed Triple for the treatment of COPD in both the U.S. and EU by the end of 2016.

May 23, 2016

Sunovion Pharmaceuticals reported results of a post-hoc analysis of a long-term safety study evaluating Brovana (arformoterol tartrate) Inhalation Solution in people with moderate-to-severe chronic obstructive pulmonary disease (COPD). Data for this post hoc analysis came from a multicenter, randomized, double-blind, 52-week safety trial. The Brovana group reported a greater reduction in hospitalization risk relative to placebo, and these results were more pronounced in a subset of patients who were responders on the St. George’s Respiratory Questionnaire (SGRQ). For the intent-to-treat population, the adjusted annualized hospitalization rate was significantly reduced with Brovana compared with placebo (relative risk=0.60 [95% confidence interval (CI)=0.41, 0.87; p=0.007]). For those patients who were SGRQ responders, the adjusted relative risk was the lowest at 0.34 (95% CI=0.12, 0.99; p=0.048); SGRQ non-responders had an adjusted relative risk of 0.81 (95% CI=0.39, 1.67; p=0.573). Brovana is approved by the FDA for the long-term maintenance treatment of bronchoconstriction in people with COPD, including chronic bronchitis and emphysema.

October 12, 2015

Afferent Pharmaceuticals has released
results of a phase IIb study of AF-219 in
chronic cough patients. The 29-patient, randomized,
double-blind, placebo-controlled
crossover study was conducted at 10 clinical
sites in the U.S. Those in the treatment
group received AF-219 50mg, followed by a
titration up to 100mg, 150mg and 200mg,
with each dose given twice daily for four
days. Patients were then crossed over to the
alternate arm of the study and treated with
either AF-219 or placebo for 16 more days.
All AF-219 doses, including the lowest dose
of 50mg twice daily, demonstrated a statistically
significant reduction in awake cough
frequency compared to placebo (p=0.002).
AF-219 was generally well-tolerated. The
incidence of decreased taste acuity, as
observed in the first study at 600mg twice
daily, was much less at the 50mg dose. Only
one patient discontinued treatment at any
dose in the current study, due to the taste
effect.

August 24, 2015

Boehringer Ingelheim has reported results
of a phase IIIb study of Spiolto Respimat
(tiotropium/olodaterol) for chronic obstructive
pulmonary disease (COPD). OTEMTO 1&2
build on the pivotal phase III TONADO trials
that demonstrated Spiolto Respimat provides
significant improvements in lung function, quality
of life, breathlessness and reduction in rescue
medication use over Spiriva Respimat right from
the initial disease stages when patients first need
maintenance therapy. OTEMTO 1&2 are part of
the >15,000 patient TOviTO phase III clinical trial
program. OTEMTO trials show Spiolto Respimat
provides clinically meaningful improvements in
breathlessness compared to placebo (measured
by a 1.62 point improvement in Transition
dyspnoea index focal score); consistent improvements
in lung function, breathlessness and
quality of life compared to Spiriva (tiotropium);
and a safety profile similar to Spiriva or placebo.
Incidence of adverse events (AEs) was broadly
similar across treatment groups, with a higher
incidence of AEs leading to discontinuation in
the placebo groups compared to the treatment
groups. The FDA recently accepted for review an
sNDA to include the OTEMTO quality-of-life data
in the Stiolto Respimat label.

June 2, 2014

GlaxoSmithKline released results of a
late-stage trial of umeclidinium (UMEC)
added to combination medicine fluticasone
proprionate and salmeterol (FSC) for
treatment of chronic obstructive pulmonary
disease. The 12-week, randomized, double-blind,
parallel-group study enrolled 600
subjects randomized 1:1:1 to once-daily
UMEC 62.5mcg, UMEC125mcg or placebo,
added to FSC (250/50mcg twice daily).
Compared with placebo added to FSC
250/50mcg, both doses of UMEC (62.5mcg
and 125mcg) added to FSC 250/50mcg
demonstrated statistically significant
improvements in trough FEV1 at day 85
(62.5 mcg=147mL; 125 mcg=138mL both
p<0.001) and zero to six-hour WM FEV1 at
day 84 (62.5 mcg=164mL; 125 mcg=160mL;
both p<0.001). During weeks one to 12 for
both the UMEC added to FSC groups, rescue
albuterol use was reduced by an average of
0.3 puffs/day compared with placebo added
to FSC (both p<0.05). Patients in the UMEC
added to FSC treatment groups experienced,
on average, a greater percentage
of rescue-free days and greater increases
from baseline in percentage of rescue-free
days (62.5 mcg= 59.4% and 13.3%; 125
mcg=56.1% and 11.1%, respectively) compared
with placebo added to FSC (49.7%
and 4.9%, respectively).

September 30, 2013

Theravance reported results of a phase IIb study of TD 4208, an investigational long-acting muscarinic antagonist (LAMA), administered once a day as a nebulized aqueous solution in patients with moderate to severe chronic obstructive pulmonary disease (COPD). The randomized, double-blind, multicenter, placebo-controlled study enrolled 62 patients randomized to receive four of six doses of TD 4208 (22mcg, 44mcg, 88mcg, 175mcg, 350mcg or 700mcg) and placebo once daily via a nebulizer during five seven-day study periods in an incomplete crossover study design. TD 4208 met the primary efficacy endpoint for all doses, and demonstrated a statistically significant change v. placebo from baseline in trough FEV1. The dose of 175mcg was identified as the lowest that demonstrated a clinically meaningful change in FEV1 v. placebo at trough of 114mL (95% CI: 76,153). Serial FEV1 measurements over 24 hours on day seven demonstrated comparable bronchodilation over the first and second 12-hour periods. TD 4208 demonstrated a low peak to trough ratio for TD 4208 consistent with a once-a-day dosing regimen. TD 4208 pharmacokinetics demonstrated low (sub-pharmacologic) and predictable systemic exposure following dosing.

September 16, 2013

Boehringer Ingelheim released results of phase III trials of olodaterol 5μg and 10μg delivered once daily via the Respimat inhaler for the treatment of moderate to very severe chronic obstructive pulmonary disease (COPD). Olodaterol was administered to 3,500 patients with COPD, including chronic bronchitis and/or emphysema. These data are from two sets of replicate, 48-week pivotal studies evaluating the long-term efficacy and safety of once-daily olodaterol in 5μg and 10μg doses, as well two sets of replicate, six-week studies investigating olodaterol’s 24-hour bronchodilation profile. In one set of 48-week, phase III pivotal studies, olodaterol 5μg and 10μg delivered once daily provided statistically significant improvements in lung function, as measured by FEV1, v. placebo plus usual care (P<0.05; n=613 and 635). In a second set of 48-week studies, the same dose and delivery of olodaterol provided comparable improvements in lung function compared to 12μg formoterol twice daily (n=904 and 934). After 24 weeks of treatment, both doses of olodaterol and formoterol provided statistically significant improvements in FEV1 AUC0-3. Olodaterol 5μg was shown to provide significant improvement (P<0.0001) in lung function within five minutes following the first dose. COPD patients had less need for both day- and night-time rescue medication when using both olodaterol delivered once daily and formoterol v. placebo over the 48-week treatment period (P<0.01). The most common adverse reactions were nasopharyngitis, dizziness, rash and arthralgia.

May 6, 2013

Almirall and Forest Laboratories issued results from a phase III trial of aclidinium bromide and formoterol fumarate for the treatment of moderate to severe chronic obstructive pulmonary disease. This 24-week, randomized, double-blind study enrolled 1,729 patients with COPD. Subjects received 400/6mcg and 400/12mcg fixed doses of aclidinium bromide/formoterol fumarate, or aclidinium bromide 400mcg alone, formoterol fumarate 12mcg alone or placebo, administered twice daily through the Genuair/Pressair inhalers. Results showed that both combinations of aclidinium/formoterol (400/6mcg and 400/12mcg given twice a day) demonstrated statistically significant improvements in the co-primary endpoints of change from baseline in morning pre-dose trough FEV1 versus formoterol 12mcg alone and in FEV1 at 1 hour post-dose versus aclidinium 400mcg alone at week 24. For the second co-primary endpoint of change from baseline in FEV1 at 1 hour post-dose versus aclidinium 400mcg, aclidinium/formoterol 400/6mcg and 400/12mcg demonstrated statistically significant improvements versus aclidinium 400mcg (69mL and 125mL, respectively) and placebo (244mL and 299mL, respectively). Both fixed-dose combination treatment arms were well tolerated in this study. The most frequent adverse events were nasopharyngitis and back pain. Based on these results, and expected results from a second phase III trial, Almirall and Forest Laboratories will file an NDA with the FDA and an MAA to the EMA.

September 10, 2012

Boehringer Ingelheim released results from a phase II adjunctive trial of tiotropium for the treatment of chronic obstructive pulmonary disease (COPD). This randomized, double-blind, four-period, crossover study enrolled 232 patients with post-bronchodilator FEV1 of ≥30% and <80% of predicted normal. Subjects received tiotropium 1.25μg, 2.5μg or 5μg in combination with olodaterol 5μg or 10μg, or olodaterol and placebo, for four weeks. Results showed the free combination of tiotropium and olodaterol provided an average lung function improvement of up to 342mL over the first six hours after four weeks of treatment (FEV1 AUC0-6) compared to pre-dose lung function mean baseline values and improvements in trough FEV1 of up to 166mL, compared to pre-treatment FEV1 mean baseline values. Tiotropium was well tolerated. The most frequent adverse events were nasopharyngitis and COPD. This study completes a comprehensive phase II program to thoroughly investigate different doses of each active component to identify the appropriate doses for the fixed-dose combination.

Elevation Pharmaceuticals issued results from a phase IIb trial of EP-101 for the treatment of chronic obstructive pulmonary disease (COPD). This randomized, placebo-controlled, double-blind, seven-arm, four-period cross-over, block design, dose-ranging study, GOLDEN-1, enrolled 140 patients with moderate to severe COPD. Subjects received EP-101 25μg, 50μg, 100μg or 200μg daily or placebo for seven days. Data demonstrated that all doses of EP-101 showed a rapid onset, dose-related, statistically significant improvement in lung function compared to placebo. Improvements in lung function with EP-101 doses were comparable to those of once-daily tiotropium dry powder inhaler and three-times daily nebulized ipratropium administered via jet nebulizer. The drug was well tolerated. The most frequent adverse events were cough and headache. Elevation Pharmaceuticals will be initiating a second phase IIb study in Q4 2012 to select the dose for phase III studies.

September 3, 2012

MediciNova reported preliminary results from a phase Ib trial of MN-221 for the treatment of chronic obstructive pulmonary disease (COPD). This randomized, placebo-controlled study enrolled 25 patients with stable, moderate-to-severe COPD. Subjects received six intravenous infusions of 1200µg MN-221 or placebo over four days. Results indicate moderately improved pulmonary function (FEV1) in MN-221 recipients, but not the placebo recipients. Moreover, the improvement of FEV1 on subsequent MN-221 dosing days was as good as or better than on day one. In addition, there was no significant ccumulation of plasma MN-221 over the multiple dosing intervals. The drug was well tolerated. Two MN-221 recipients with pre-existing heart disorders were terminated from the study due to transient arrhythmias identified by electrocardiograph monitoring that did not have clinical symptoms or consequences and resolved spontaneously. MediciNova will meet with the FDA in October for an end-of-phase II meeting.

May 21, 2012

Elevation Pharmaceuticals released results from a phase IIb trial of EP-101 for the treatment of chronic obstructive pulmonary disease (COPD). This randomized, placebo-controlled, double-blind, seven-arm, four-period cross-over, incomplete block design, dose-ranging study enrolled 140 patients. All doses of EP-101 met the primary endpoint of superior efficacy versus placebo as measured by improved lung function (24-hour trough forced expiratory volume in one second [FEV1] [p<0.0005] and FEV1 AUC 0-24 [p<0.0001]) on day seven following administration of EP-101 via the eFlow nebulizer. EP-101 was well-tolerated with a safety and side effect profile comparable to placebo and two active comparators. Patients experienced a robust magnitude and duration of bronchodilation comparable to the active comparators, a rapid onset of action (approximately five minutes) and a fast treatment time of less than three minutes. Elevation will initiate a second phase IIb study later in 2012 to select the optimal dose of EP-101 for study in the pivotal phase III program.

April 30, 2012

Novartis released results from a phase III trial of QVA-149 for the treatment of chronic obstructive pulmonary disease. The 26-week, multi-center, randomized, double-blind, double-dummy, parallel-group study, ILLUMINATE, enrolled approximately 500 subjects with moderate to severe disease. The primary objective was to demonstrate the superiority of once-daily QVA149 versus twice-daily Seretide (fluticasone/salmeterol) in terms of forced expiratory volume in one second area under the curve for 0-12 hours. Data demonstrated that superior lung function (p<0.001) was achieved with QVA149 over Seretide in this population.

April 9, 2012

Novartis released results from three phase III trials of QVA149 for the treatment of chronic obstructive pulmonary disease (COPD). SHINE was a 26-week, multicenter, randomized, double-blind, parallel-group, placebo and active controlled pivotal trial in 2,144 subjects with moderate to severe COPD. The trial met the primary endpoint by demonstrating the superiority in trough FEV1 (p<0.001) of once-daily QVA149 compared to once-daily indacaterol or once-daily NVA237. QVA149 also showed superiority in trough FEV1 (p<0.001) compared to placebo and open-label tiotropium (18 mcg). BRIGHT was a double blind, randomized trial in 85 subjects. The primary endpoint was the effect of QVA149 compared with placebo on exercise tolerance, measured at three weeks. The subjects treated with QVA149 experienced significantly better exercise endurance versus placebo (p≡0.006). ENLIGHTEN was a 52-week randomized, double-blind, parallel-group, placebo controlled study in 339 subjects with moderate to severe COPD. The trial was designed to evaluate the long-term safety of once-daily QVA149 versus comparator over one year. QVA149 was well tolerated with a safety and tolerability profile similar to placebo.

November 21, 2011

Theravance reported results from a phase IIa trial of TD-4208 for the treatment of chronic obstructive pulmonary disease (COPD). This randomized, double-blind, four-period crossover study enrolled 32 subjects with moderate to severe COPD. The subjects were randomized to receive TD-4208 (350 mcg and 700 mcg), ipratropium bromide, and placebo, each administered as single doses via a nebulizer for four doses. The primary endpoint of the study was mean change from baseline in peak FEV1 compared to placebo. Both doses of TD-4208 and the active control ipratropium bromide demonstrated a statistically significant improvement in peak FEV1 versus placebo of 174 mL, 169 mL and 176 mL, respectively (p<0.001). All three treatments demonstrated a rapid and similar onset of action. Both doses of TD-4208 demonstrated a long duration of action with statistically significant effect at 24 hours. TD-4208 doses were generally well tolerated. The most common adverse events were headache and dyspnea.

September 5, 2011

Pearl Therapeutics issued results from a phase II trial of formoterol fumarate metered dose inhaler (PT005) for chronic obstructive pulmonary disorder. The randomized, double-blind, single dose, six-treatment, placebo-controlled, crossover trial enrolled approximately 48 subjects with moderate to severe COPD. The subjects received one of three doses of PT005, Foradil Aerolizer (standard of care) or placebo. The primary endpoint was improvement in lung function assessed by FEV1 AUC0-12 from test day baseline. All doses of PT005 produced highly statistically significant improvements in lung function compared to placebo (p<0.0001). An increase in efficacy was associated with increasing doses and the two lower doses tested were comparable to 12 mcg Foradil Aerolizer, the currently approved dose.

July 4, 2011

Novartis issued results from a phase III trial of NVA237 for the treatment of chronic obstructive pulmonary disease. This 52-week, double-blind, placebo-controlled, parallel-group study, GLOW2, enrolled 1,066 subjects with moderate to severe COPD. The subjects were randomized into three treatment arms: once-daily NVA237 50 mcg, placebo, or once-daily open-label tiotropium (Spiriva) 18 mcg. The primary endpoint was reached with NVA237 demonstrating superior 24-hour bronchodilation over placebo at 12 weeks, measured by trough FEV1 (forced expiratory volume in one second), Efficacy was similar to tiotropium. Key secondary endpoints were also reached, including improvement in breathlessness, improved quality of life, time to first COPD exacerbation and the use of rescue medication.

June 6, 2011

GlaxoSmithKline and Theravance issued results from two phase III trials of Relovair for chronic obstructive pulmonary disease (COPD). These placebo-controlled, double-blind, parallel-group studies enrolled approximately 2,200 subjects with moderate to severe COPD. The subjects received either fluticasone furoate (FF) alone (100mcg, 200mcg), vilanterol (VI) alone (25mcg), Relovair (50, 100, or 200mcg FF plus 25mcg VI) or placebo. Two separate measures of lung function were evaluated: improvements in lung function over the first four hours post dose on day 168 and the end of dose trough lung function on day 169. Both studies showed statistically significant improvements for Relovair compared with placebo on 0-4 hour weighted mean FEV1 and trough FEV1. Relovair was well tolerated and the most common adverse event was nasopharyngitis.

April 25, 2011

Novartis released initial results from a phase III trial of NVA237 as a once daily treatment for chronic obstructive pulmonary disease (COPD). The 26-week, randomized, double-blind, placebo-controlled trial, GLOW1, enrolled approximately 800 subjects who received NVA237 (50g) or placebo once daily. The trial met its primary endpoint by demonstrating superior bronchodilation to placebo at 12 weeks, as measured by trough FEV1 (p<0.001). The incidence of adverse events was similar in the NVA237 and placebo arms.

March 14, 2011

Revotar released results from a phase II trial of inhaled bimosiamose for chronic obstructive pulmonary disease (COPD). This double-blind, placebo controlled, randomized, cross-over study enrolled 77 non-smoking patients with moderate to severe COPD. The subjects received nebulized bimosiamose solution or placebo twice daily for 28 consecutive days in two subsequent periods, which were separated by a wash-out period. Bimosiamose showed a broad anti-inflammatory effect, reducing most of the evaluated sputum markers The primary endpoint, reduction in interleukin-8, was significantly reduced in sputum of the bimosiamose treated group compared to the placebo group (p<0.009). Inhalation of Bimosiamose was safe and well tolerated.

January 10, 2011

Almirall and Forest Laboratories reported results from a phase III trial of aclidinium bromide for chronic obstructive pulmonary disease (COPD). This six month double-blind placebo-controlled study. ATTAIN (Aclidinium To Treat Airway obstruction In COPD patieNts) enrolled 828 subjects with moderate to severe COPD in Europe and South Africa. The subjects received inhaled aclidinium bromide 200 μg and 400 μg, both administered twice daily, or placebo. The primary endpoint was met. Aclidinium 200g and 400g produced statistically significant increases from baseline in morning pre-dose (trough) FEV1 versus placebo at week 24 (99mL and 128mL, respectively; p<0.0001). Aclidinium also demonstrated statistically significant improvement over placebo on the three secondary endpoints assessed in the study: changes from baseline in peak FEV1 observed after morning dosing the percentage of patients experiencing a clinically meaningful improvement from baseline in shortness of breath and the percentage of patients achieving improvement from baseline in health related quality of life.

December 6, 2010

Pearl Therapeutics reported positive results from a phase IIb trial of PT003 for the treatment of chronic obstructive pulmonary disease (COPD). This randomized, double-blind, four-period, eight-treatment, placebo-controlled, cross-over study enrolled 118 subjects with moderate to very severe COPD. The trial was designed to compare the efficacy and safety of two doses of PT003 to its' individual components (PT001 and PT005), placebo and two active comparators (tiotropium bromide- Spiriva Handihaler and formoterol fumarate- Foradil Aerolizer). PT003, PT001, PT005 and placebo were administered twice daily (BID) for one week while Spiriva and Foradil were administered according to their approved label: 18 ug once daily and 12 ug BID, respectively, each for one week. The primary endpoint was change in forced expiratory volume in one second (FEV1) area under the curve from 0 to 12 hours from baseline to Day 7. Both doses of PT003 were superior to Spiriva (p<0.0001), Foradil (p<0.0002), placebo (p<0.0001), PT001 (p<0.0001) and PT005 (p<0.0001). The trial also assessed Peak FEV1 on days one and seven, which measures the maximum improvement in lung function observed during the assessment period. Both doses of PT003 were superior to Spiriva and Foradil on day one (p<0.03), with further benefit observed on day seven (p<0.002).

November 8, 2010

Forest Laboratories and Almirall reported positive results from a phase III trial of inhaled aclidinium bromide for the treatment of chronic obstructive pulmonary disease. This randomized, double-blind, placebo-controlled study enrolled 544 subjects with mean baseline Forced expiratory volume in one second (FEV1) at randomization ranging from 1,262 to 1,447mL. The subjects received placebo or aclidinium bromide 200ug or 400ug twice daily for 12 weeks. The primary endpoint was the improvement in FEV1 from baseline to week 12. This improvement was statistically significant in both the 200ug (p≡0.019) and 400ug (p≡0.001) dose groups compared to placebo. Aclidinium was well tolerated.

May 24, 2010

Pearl Therapeutics reported positive results from two phase IIa trials of PT003, a fixed dose combination of glycopyrrolate and formoterol for chronic obstructive pulmonary disease (COPD). Study PT0050801: This randomized, double-blind, 5-period, placebo and active-controlled, cross-over study enrolled 34 subjects who received placebo, a single administration of three doses of PT003 (2.4, 4.8 and 9.6 micrograms) or open label Foradil Aereolizer, 12 micrograms. All three doses of PT003 demonstrated superior efficacy compared to placebo in terms of FEV1 at 12 hours, the primary endpoint of the study (p<0.05). In addition, the 9.6 microgram dose of PT003 demonstrated non-inferior efficacy relative to Foradil over the 12-hour period (p<0.001) and at every individual time point assessed (p<0.05). Study PT0010801: This randomized, double-blind, single dose, four-period, six-treatment, placebo-controlled, cross-over, ascending dose study treated 30 subjects who received placebo, four doses of PT003 (18, 36, 72 and 144 micrograms) or open label Spiriva Handihaler (18 micrograms). All four doses of PT003 demonstrated superior efficacy compared to placebo in terms of Peak FEV1, the primary endpoint of the study (p≡0.003). In addition, the 72 and 144 microgram doses of PT003 demonstrated non-inferior efficacy relative to Spiriva. There were no substantial differences noted between the PT003, Foradil/Spiriva and placebo treatment arms.

March 29, 2010

MediciNova reported positive preliminary results from a phase Ib trial of MN-221 for the treatment of chronic obstructive pulmonary disease (COPD). This randomized, placebo-controlled, dose escalation study enrolled 48 subjects with stable, moderate to severe COPD. The subjects received a one-hour intravenous infusion of MN-221 at one of three escalating dose levels (300, 600 or 1200 micrograms) or placebo. All doses of MN-221 demonstrated significant improvements in percent change in forced expiratory volume in one second (FEV(1)). as compared to the baseline and placebo. At the end of the one hour infusion, FEV(1) increased as compared to baseline by an average of 21.5% (p≡0.0025) for the 1200 microgram dose, 16.2% (p≡0.020) for the 600 microgram dose, and 9.2% for the 300 microgram dose compared to a decrease of 4.0% for the placebo. MN-221 at doses of 600 micrograms and 1200 micrograms appeared to have an effect for at least six hours as compared to placebo. The treatment was well tolerated.

January 18, 2010

Almirall and Forest Labs issued positive results from a phase III trial of aclidinium bromide for chronic obstructive pulmonary disease (COPD). This 12-week randomized, double-blind, placebo controlled trial, dubbed ACCORD COPD I, enrolled 561 subjects with moderate to severe COPD across North America. The subjects received aclidinium bromide 200g or 400g or placebo, administered twice daily by inhalation. The primary endpoint was the change from baseline in morning pre-dose (trough) forced expiratory volume in 1 second (FEV1) versus placebo at week 12. This endpoint was reached with statistical significance. The changes from baseline values compared to placebo were 86mL and 124 mL for the 200g and 400g groups, respectively, (p<0.0001). Both doses of aclidinium bromide also produced a significant change from baseline versus placebo in peak FEV1, the secondary endpoint, as early as day one which was sustained for the duration of the study.

June 29, 2009

Osiris released positive interim results from a phase II trial of Prochymal stem cell therapy for the treatment of chronic obstructive pulmonary disease (COPD). This double-blind, placebo-controlled study enrolled 62 subjects with moderate to severe COPD. The subjects were randomized to receive four infusions of either Prochymal or placebo, both with standard of care, and will be followed for two years. The endpoints are improvements based on pulmonary function tests, exercise capability, and quality of life. These data are from six months following initial infusion. Prochymal significantly decreased the levels of inflammation, as measured by C-reactive protein (CRP) compared to placebo in subjects with elevated CRP (>4 mg/L) at the time of study entry (p<0.05). The difference from placebo was evident at ten days post initial infusion, and was maintained throughout the treatment and follow-up period. However, pulmonary function tests such as forced expiratory volume in one second (FEV1) were not improved over placebo following treatment with Prochymal at six months. All subjects completed the planned course of four infusions without any evidence of infusional toxicity and adverse events were comparable between the two arms.

January 5, 2009

GlaxoSmithKline and Theravance issued positive results from a phase IIb trial of GW642444 for the treatment of chronic obstructive pulmonary disease (COPD). This randomized, double-blind, placebo-controlled study enrolled 605 subjects who received one of five doses of GW642444, (3, 6.25, 12.5, 25 and 50 mcg) or placebo, administered once daily via a novel inhaler, for four weeks. All subjects were permitted to use rescue medication (albuterol) as needed. The primary endpoint was efficacy, assessed by the change in trough (23-24 hour) Forced expiratory volume in one second (FEV1) from baseline after 28 days. All doses achieved statistically significant increases in lung function (trough FEV1) compared to placebo (p<0.05). The changes were dose-dependent with the two highest doses exceeding a predefined threshold of 130 mL increase in FEV1 at trough. This effect was rapid and dose-dependent and was sustained over 24 hours. Improvements in lung function 24 hours after the first dose were maintained throughout the 28-day treatment period. GW642444 was well tolerated at all doses and the frequency of adverse events was comparable to placebo. Based on the results, the companies plan to move forward with the development of GW642444.

September 8, 2008

Almirall and Forest Laboratories issued pooled results from two phase III trials of aclidinium bromide for the treatment of chronic obstructive pulmonary disease. These double-blind, multicenter, parallel-group, placebo-controlled studies, dubbed ACCLAIM/COPD I (conducted in Europe) and ACCLAIM/COPD II (conducted in North America), enrolled a total of 1,647 subjects with moderate-to-severe COPD. The subjects were randomized to receive aclidinium bromide (200 micrograms once daily) or placebo over a one-year treatment period. The primary endpoint for both trials was bronchodilation at the end of the dosing interval, assessed as trough forced expiratory volume in one second (FEV1), and measured at 23-24 hours post-dose. In both studies aclidinium bromide demonstrated a significant difference versus placebo in trough FEV1 at 12 weeks (p-value <0.001) and 28 weeks (p-value <0.001). This effect was maintained over one year (p-value <0.001). The improvement in the trough FEV1, at weeks 12 and 28, of aclidinium arms compared to placebo was in the range of 60 to 70 mL in both trials. The change from baseline in peak FEV1 observed after dosing aclidinium compared to placebo at 12 and 28 weeks was between 154 and 177 mL (p-value <0.0001), with a median time to peak of two hours. Secondary endpoint results demonstrated that aclidinium significantly delayed the time to the first moderate to severe exacerbation in ACCLAIM/COPD II (p-value=0.01). These results were not significant in ACCLAIM/COPD I. In the pooled analysis of both studies, there was a positive trend in delaying the time to first moderate or severe exacerbation (p-value=0.054). Based on the results, Almirall and Forest Labs plan to move forward with the development of aclidinium bromide.

April 14, 2008

MAP Pharmaceuticals released positive results from a phase IIa trial of MAP-0005 for the treatment of asthma and chronic obstructive pulmonary disease (COPD). This randomized, open-label, active-controlled, crossover, safety and dose response study enrolled fifteen adult subjects. The subjects received two different emitted doses of MAP0005, 104/5.4 mcg and 312/16.2 mcg, or a 160/9 mcg dose of the leading currently approved product. Maximum change in forced expiratory volume in one second (FEV1) was similar for all three treatments, as was time to maximum change in FEV1. Plasma levels of budesonide were dose proportional for MAP0005. No serious or unexpected adverse events were reported in the study, and MAP0005 was well tolerated. Based on the results, MAP plans to move forward with the development of MAP-005.

December 10, 2007

Takeda reported positive results from a trial of ramelteon for the treatment of insomnia in subjects with Chronic Obstructive Pulmonary Disease (COPD). This double-blind, placebo-controlled trial enrolled twenty-five subjects with moderate to severe COPD. The subjects were randomized to receive ramelteon 8 mg or placebo thirty minutes before overnight monitoring of oxygen saturation (SaO2) by pulse oximetry and sleep by polysomnography. After a five- to ten-day washout, subjects crossed over to the alternate treatment and repeated the procedure. The primary endpoint was mean SaO2 for the entire night. Data revealed that ramelteon did not exacerbate respiratory depressant effects; there was no statistically significant difference in SaO2 for the entire night observed between the ramelteon arm and the placebo arm (92.2% versus 92.4%, p=0.576). Secondary endpoints were reached as well. There was no statistically significant difference in the number of minutes in the night that SaO2 was <80% and <90% (p=0.927 and p=0.653, respectively). A significant increase in total sleep time (389.0 minutes versus 348.4 minutes, p=0.019) and sleep efficiency (81.0% versus 72.6%, p=0.019) was observed with ramelteon compared to placebo. Latency to persistent sleep was shorter with ramelteon (23.1 minutes) compared to placebo (56.9 minutes; p=0.051). Based on the results, Takeda plans to continue with the development of ramelteon for this indication.

November 5, 2007

Revotar issued positive preliminary results from a phase IIa trial of bimosiamose, an inhalation therapy for the treatment of Chronic Obstructive Pulmonary Disease (COPD). This open label trial enrolled fourteen subjects with stable COPD, stage 0 to II, in Germany. The subjects inhaled 70 mg of Bimosiamose twice a day, for up to nine days. After nine days of treatment, the investigators conducted an analysis of induced sputum. Data showed that bimosiamose significantly decreased both the relative and absolute lymphocytes count, as well as sputum IL-8. Treatment was determined to be safe and well tolerated. Based on the results, Revotar plans to move forward with the development of bimosiamose for this indication.

August 13, 2007

Epix announced positive results from a phase IIa trial of PRX-08066 for the treatment of pulmonary hypertension associated with chronic obstructive pulmonary disease (COPD). This randomized, double-blind, placebo-controlled trial enrolled 71 subjects who received 200 mg of PRX-08066 once-daily; 400 mg of PRX-08066 once-daily or placebo. This two week double-blind phase was followed by an open-label extension phase in which 10 subjects received 200 mg of PRX-08066 daily for six weeks. A statistically significant dose response was observed in the decrease of 4mmHg or more in post-exercise systolic pulmonary artery pressure (SPAP) (p=0.036). In the 400 mg dose group, 45% of the subjects had a reduction in post-exercise SPAP of 4mmHg or more versus 14% on placebo (p=0.043). The median reductions were 1.1 mmHg and 3.37 mmHg in the 200 mg and 400 mg dose groups, respectively, compared with no change on placebo (p=0.08 for high dose versus placebo). Treatment was well tolerated and no effect on systemic blood pressure was observed. Based on the results Epix plans to advance PRX-08066 into further trials.

March 19, 2007

Pharmaxis announced mixed results from a phase II trial of Aridol for thetreatment of chronic obstructive pulmonary disease (COPD). This trial enrolled79 subjects in Australia. The primary endpoint was to determine if subjectsthat were positive to an Aridol challenge test would demonstrate an improvementin lung function, as measured by spirometry, following a 3 month course oftherapy. This endpoint was not met. However the secondary endpoint, the effectof inhaled corticosteroids on hyper-responsive airways as measured by apositive Aridol test, was met. Treatment led to a statistically significantimprovement in hyper-responsive airways (p< 0. 004). Based on the results,Pharmaxis plans to initiate a larger study in Switzerland in April of 2007.

July 3, 2006

Novartis, under license from Sosei and Vectura, reported positive results of a phase IIb trial of NVA237 for the treatment of chronic obstructive pulmonary disease (COPD). This double-blind, parallel group, placebo controlled study enrolled 335 subjects across 35 European sites, who received one of four doses of the drug or placebo once daily, or an approved open-label regimen of tiotropium, for 28 days. Results from the study demonstrated statistically significant bronchodilatory efficacy in a number of measures of pulmonary function, including the primary endpoint (trough FEV1). The drug was generally well tolerated, and no marked differences were noted in rates or severity of adverse events between the drug and placebo or tiotropium.

May 30, 2005

Novartis announced positive results of a pair of phase II trial of their investigational bronchodilator indacaterol (QAB149), for the treatment of asthma and chronic obstructive pulmonary disease (COPD), at the Centenary Meeting of the American Thoracic Society. Results form the first study indicated that the drug produced effective dose-dependent 24-hour bronchodilation within 5 minutes of administration, and had a safety and tolerability profile comparable to placebo. The second study indicated a positive cardiovascular safety profile, with no observed impact on ECG readings, mean QTc interval, vital signs, of laboratory results. Both studies were randomized, double-blind, placebo-controlled trials. The first was a dose-ranging study which enrolled 42 patients with intermittent or mild to moderate persistent asthma, who received one of four doses of the drug (50 mcg, 100 mcg, 200 mcg, or 400 mcg) or placebo once daily. The second was a multi-center parallel- group safety and tolerability study which enrolled 156 subjects.

March 28, 2005

Icos reported results of a phase II trial of their investigational phosphodiesterase-4 (PDE4) inhibitor IC485, for the treatment of chronic obstructive pulmonary disease (COPD). Data from all dosing cohorts failed to demonstrate superiority in improving lung function vs. placebo, the trial’s primary endpoint. This double-blind, placebo-controlled study enrolled 258 COPD patients, who received one of three doses of the drug or placebo. Following these results, the company announced that it did not intend to continue development of IC485, but did still intend to pursue the development of other PDE4 inhibitors in their pipeline.

May 28, 2002

Phase II trial results indicate that one-fifth of the standard ipratropium dose administered via Aerogen's Aerodose ipratropium inhaler produces similar lung function improvement as a full dose with the Pari LC Plus jet nebulizer. The trial evaluated change in lung function (forced expiratory volume in one second (FEV1)) in subjects with chronic obstructive pulmonary disease. No drug- or device-related adverse events were reported.

Phase III data indicates that severe sepsis patients with pulmonary complications have a greater likelihood of survival with Eli Lilly's Xigris (drotrecogin alfa (activated)) treatment compared to treatment with standard care alone. The results were obtained from an analysis of two subsets in the PROWESS trial: subjects with severe sepsis who were on mechanical ventilation and severe sepsis subjects with chronic obstructive pulmonary disease (COPD). At day 28, a significantly higher number of Xigris-treated subjects were off ventilation (65.5%) compared to subjects receiving standard care (61%). Additionally, Xigris treatment significantly increased the survival rates for subjects independent of their ventilator status. Regarding COPD, an analysis of 408 severe sepsis subjects with COPD showed a 36% reduction in the risk of death with Xigris treatment compared to treatment with standard care.